Process of manufacturing organo-phosphorous derivatives

ABSTRACT

A process of manufacturing organo-phosphorous derivatives is described herein. The process involves first forming a solution of sodium bisulfide in situ by reacting a sodium compound with hydrogen sulfide in the presence of a solvent. Then, a solution is formed consisting of tetrahydrofuran and Nhalomethylphthalimide which is reacted with the sodium bisulfide solution to form N-mercaptomethylphthalimide. The Nmercaptomethylphthalimide is then isolated and reacted with a dialkylphosphorodithioic acid and an aldehyde to form a compound of the following formula:   WHEREIN R and R&#39;&#39; can each be selected from a lower alkyl group having from 1 to 5 carbon atoms or a lower alkoxy group having from 1 to 5 carbon atoms.

United States Patent [1 1 Fancher et al.

[4 1 Sept. 18,1973

[ PROCESS OF MANUFACTURING ORGANO-PIIOSPIIOROUS DERIVATIVES [75]inventors: Llewellyn W. Fancher, Orinda; Jules Kalbfeld, Pinole, both ofCalif.

[73] Assignee: Stauffer Chemical Company, New

York, NY.

[22] Filed: Aug. 12, 1971 [21] App]. No.: 171,378

Related U.S. Application Data [63] Continuation-impart of Ser. No.868,580, Oct. 22,

1969, abandoned.

[52] U.S. Cl. 260/326 E, 424/200 [51] Int. Cl C07d 27/52 [58] Field ofSearch 260/326 E Wagner et al. Synthetic Organic Chemistry (1953) p.778.

Primary Examiner-Joseph A. Narcavage AttorneyDaniel C. Block et al.

[57] ABSTRACT A process of manufacturing organo-phosphorous derivativesis described herein. The process involves first forming a solution ofsodium bisulfide in situ by reacting a sodium compound with hydrogensulfide in the presence of a solvent. Then, a solution is formedconsisting of tetrahydrofuran and N- halomethylphthalimide which isreacted with the sodium bisulfide solution to formN-mercaptomethylphthalimide. The N-mercaptomethylphthalimide is thenisolated and reacted with a dialkylphosphorodithioic acid and analdehyde to form a compound of the following formula: I

wherein R and R can each be selected from a lower alkyl group havingfrom 1 to 5 carbon atoms or a lower alkoxy group having from 1 to 5carbon atoms.

4 Claims, No Drawings 1 PROCESSIOF MANUFACTURING ioRoANomIIosPIIoRousDERIVATIVES CROSS REFERENCE TO RELATED APPLICA- TION This application isa continuation-in-part of copending application Ser.'No. 868,580, filedOct. 22, 1969,

entitled PROCESS OF MANUFACTURING OR- =GANO-PHOSPHOROUS DERIVATlVES"andnow abandoned.

'BACK'GROUND'OF THE INVENTION In theiart of manufacturing Nmercaptoalkylphthalimideshaving at leasttwo or more carbon atoms it isthe usual practice to react'th'e'respective phthalimide alky'lhalidewith'potassium hydrosulfide. The reaction isusua'lly carriedou't atelevated'temperatures in an alcohol solvent. High yields of the endproduct are reported. A'more detailed study of'this'procedure can befound'in the'textbooks byBeilstein and'Wagner et al.

When'this procedure is employed to manufacture the methyl derivative ofthe N-mercaptoalkylphthalimide,

the end product cannot be'readily identifiedx'lhe'reao tion'between thecomponents forman agglomeration of unusable compounds. No theory orhypothesis can'be advanced for'thefailure of thisprocessto manufacturethe desired endproduct.

BRIEF "DESCRIPTION OF THE INVENTION It has been discovered thatN-mercaptomethylp'hthalimide can be manufactured in reasonable yie'ldsbyforming sodium 'bisulfide in situ by reacting sodium -methylate withhydrogen'sulfide in an alcohol solvent or in the alternative'formin'gthe sodium'bisulfideby reacting a sodium dispersion with hydrogensulfide.

Thereafter, 'N-halomethylpht halimide in tetrahydrofuran is reacted withthe sodium 'bisul fide at elevated temperatures. The'N-mercaptomethylphthalimide is then reacted with a'phosp'hor'ouscompound toform an 'organo-pho'sphorous compound.

DETAILED DESCRIPTION OF THE INVENTION lnt'he practice of the presentinvention, sodium bisulfide isfirst manufactured in situ byeitherreac'ting'sodium methylate with hydrogen sulfide or reacting asodium dispersion with hydrogen sulfide to form the sodium bisulfide.The :reactionof the sodium 'methylate with hydrogen sulfide is carriedout 'in the-presence of analcohol solvent such as methanol,ethanol,'oriso pro- .panol. Then, a solution is formed 'by dissolving N-halomethylphthalimide in tetrahydrofuran and adding to the sodiumbisulfide solution. *It is essential to the practice of the presentinvention to dissolve the N- halome thylphthalimide in tetrahydrofuranbecause other solvent systems will notiproduce the desired end product.The reaction components are-then heated up to about 60C. for asufficient length of time to form the end product. The time necessary toform the end product is usually indicatedby'the cessation of theevolu'tion of'hydroge'n'sulfide. The reaction'mixture'should, I 'be'kept under inert atmosphere to prevent formation ofdiphthalimidome'thyl 'disulfide. The reaction product is filtered andthe filtrate stripped to a residue which can be recrystallized frommethylene chloride. The halo :moiety of the N-halomethylphthalim'ide canbe selected from the group consisting of chlorine or bromine andmixtures thereof.

The compositions manufactu'redby the process of the present inventionare highly reactive intermediates to form pesticides. Thus, the Nmercaptomethylph- I thalimide can'be'further reacted with phosphorus'derivatives and an aldehyde to form insecticides, miticides andparasiticides having the following formula:

wherein R and R can each be selected from lower alkylgroups having from1 to 5 carbon atoms or lower alkoxy groups'having from 1 to carbonatoms.

The compounds encompassed by the above formula are manufactured byreactingthe appropriate dialkyl- 'phosphorodithioic acid and an aldehydewith N mercaptomethylphthalimide to provide the desired end-product.

In orderto illustrate the merits of the present invention the followingexamples are provided:

EXAMPLE I An excess of hydrogen sulfide was reacted with 684 grams ofsodium methylatein a methanol solvent to give a solution ofsodiumhydrogen'sulfide. A solution ofN chloromethylphthalimide intetrahydrofuran was prepared by adding 586.5 grams ofchloromethylph'thalim ide to 2,500 milliliters of tetrahydrofuran. TheN-cliloromethylphthalimide solutionwas'added'to the sodium hydrogensulfide solution. The components were'heatedto 45C. until no furtherhydrogen sulfide was given off. The reaction product was filtered,stripped and 'rec'rystalliied with methylene chloride. The

yield-was 62 percent.

"EXAMPLE [I dispersion. A warm-water bath was brought in contact withthe reactor. The reactor was kept warm until no further hydrogen sulfidewas observed. The mixture was stripped of tetrahydrofuran, the residuetaken up in-diethyl ether and allowed to 'stand overnight. The reactionproduct was stripped and identified as N-mercaptomethylphthalimide in anamount of 42.5

percent yield.

EXAMPLE III An excess-of'hyd'rogensulfide was reacted with 4,320 ml. of25% sodium methylate in a methanol solvent to get a solution of sodiumhydrogen sulfide. Using the methanol as a'solven't, l ,955 mg. ofch'loromethyl phthaliini'de were added as solids to this solution.No'identifi'able product could be 'found fro'm this reaction.

EXAMPLE IV The procedure as outlined in Example 111 was repeated in itsentirety except 3.9 g. of N- chloromethylphthalimide were added assolids. No reaction took place.

EXAMPLE V The process as outlined in Example 111 was repeated in itsentirety' except the N-chloromethylphthalimide was'dissolved intetrahydrofuran at 1.5 mls. per mg. and allowed to react over theweekend. The melting point of the crude product was 126-136. The productwas filtered and stripped to a residue to provide 65 percent yield ofthe desired product.

EXAMPLE VI A sodium dispersion, 0.865 mls. was charged to a 50 ml.reactor. The precipitate was washed in with 5 ml. of toluene as asolvent. Hydrogen sulfide was passed over the surface until nomore'hydrogen was liberated from the mixture. Then, 0.977 g. of N-chloromethylphthalimide were charged to the mixture at -67C. The batchwas allowed to warm to room temperature. The resultant product wasfiltered. No reaction took place and all the starting materials wererecovered.

EXAMPLE Vll Preparation of S-(Phthalimido-N-methylthiomethyl)0,0-diethy1-phosphorodithioate Twenty-seven and nine-tenths grams(0.15M) of diethylphosphorodithioic acid was cooled below C. and. 15.1vcc. (0.2M) 30 formalin (37%) was added with stirring and cooling below20C. The mixture was shaken with 100cc. of benzene, the aqueous layerremoved and-the benzene layer dried-over anhydrous magnesium sulfate,then filtered into a flask equipped with an apparatus for the continuousremoval of water. To the flask was added 19.2 g. (0.1M) ofN-mercaptomethylphthalimide, the stirrer was started and the mixturerefluxed for 3.5 hours. During this time 1.2 cc. of water collected inthe separator. After cooling, the mixture wasmade slightly basic withcold dilute sodium bicarbonate solution, the aqueous phase removed andthe benzene layer washed with dilute sodium chloride solution, driedover. anhydrous magnesium sulfate, filtered and evaporated to give 31.7g. (81 percent of theory) of the product as a viscous liquid, n 1.5928.

Analysis C H N S Theory 43.0 4.61 3.58 24.6 Found 44.6 4.82 3.71 25.0

As can be seen from the above examples, it is essentialto the practiceof the present invention that tetrahydrofuran be employed as a solventfor the I N- halomethylphthalimide.

The following is a list of compounds prepared according to theaforedescribed procedures. Compound numbers have been assigned to eachcompound and are. used throughout the balance of the application.

Compound No. R R n *1 OC H OC H 1.5928 2 OCH; OCH 1.5968 3 C H OCH1.6088 4 C H OC;,H-,-i 1.5793

* No. 1 prepared in Example 111 As previously mentioned, the hereindescribed composition produced in the above-described manner arebiologically active compounds which are useful and valuable incontrolling various pest organisms. The compounds of this invention weretested as miticides in the following manner.

Miticide evaluation test The two-spotted mite Tetranychus telarius(Linn.) was employed in tests for miticidal activity. Young pinto beanplants in the primary leaf stage were used as host plants. The youngpinto bean plants were infested with several hundred mites. Dispersionsof candidate materials were prepared by dissolving 0.1 gram in 10 ml. ofa suitable solvent, usually acetone. Aliquots of the toxicant solutionswere suspended in water containing 0.0175% v./v. Sponto 221, which isdescribed as a polyoxy-ethylene sorbitan monolaurate ether of alkylatedphenols blended with organic sulfonates, emulsifying agent, the amountof water being sufficient to give concentrations of active ingredientranging from 0.25 to 0.005 percent. The test suspensions were thensprayed on the infested pinto bean plants. After seven days, mortalitiesof post-embryonic and ovicidal forms were determined. The percentage ofkill was determined by comparison with control plants which had not beensprayed with the candidate compounds. The LD-SO value was calculatedusing'well-known procedures. The LD-50 values are reported under thecolumns PE and Eggs in the table below.

Systemic evaluation test This test evaluated the root absorption andupward translocation of the candidate systemic compound. The two-spottedmite, Tetranychus zelarius (Linn.), was employed in tests for systemicactivity. Young pinto bean plants in the primary leaf stage were used ashost plants. The pinto bean plants were placed in bottles containing 200ml. of the test solution and held in place with cotton plugs. Only theroots were immersed. The" solutions were prepared by dissolving thecompounds to be tested in a suitable solvent, usually acetone, and thendiluting with distilled water. The final acetone concentration neverexceeds about 1 percent. The toxicants were initially tested at aconcentration of 10 parts per million (p.p.m.). Immediately after theplants were placed in the test solutions they were infested with mites.Mortalities were determined after seven days. The percentage of kill wasdetermined by comparison with control plants which had been placed indistilled water only. The LD-50 value was calculated using wellknownprocedures. The LD-50 values in p.p.m. are reported under the columnSystemic" in Table l.

The compounds were also found to be active against I black bean aphid(Aphis fabae (Scop.)). The same test procedure as given for thetwo-spotted mite above was used for black bean aphid except thatnasturtium (Tropaeoluin sp.) plants approximately 2 to 3 inches tallwere used as the host plant.

TABLE 1 Two-Spotted Mites LD-SO BA PE Eggs Systemic Compound PercentConcentration (P.P.M.) No. 1 0.003 0.00l 0.005 8 2 0.0008 0.005 0.03 4 30.003 0.005 0.03 4 4 0.003 0.003 0.03 [0 Internal animal parasitesystemic tests The following procedure describes the chemotherapeuticefficacy tests utilized to demonstrate the animal parasitology activityof the compositions of the present invention.

Unparasitized weanling mice were offered medicated food for 1-2 daysprior to inducing infections, and for a total of 21 days infections wereadministered per os using l00-300 embryonated ova/mouse of Syphaciaobvelata (So) and 100-300 embryonated ova/mouse of Aspiculuristetraptera (At).

A suitable number of unmedicated littermate mice also received the aboveinfection and served as control to determine the comparative efficacy ofthe medications. All mice were sacrificed after 21 days (the medicationperiod) and the residual parasites found in the intestine wereidentified and counted. These counts in the medicated groups werecompared to the unmedicated (controls) and a percent efficacy wasassigned, (M/lCXlOO)lOO efficacy.

TABLE II Efficacy Dosage Compound No. (P.P.M.) So. At. 1 65 75 I00 2 12583 100 3 30 100 90 4 65 80 80 What is claimed is:

l. A process of forming an organo-phosphorous derivative comprising thesteps of:

a. Forming a sodium bisulfide solution in situ by reacting a sodiumcompound selected from a sodium dispersion, sodium methylate andmixtures thereof with hydrogen sulfide, said sodium compound being mixedwith an alcohol solvent;

b. Forming a solution of tetrahydrofuran and N- halomethylphthalimideselected from the group consisting of N-chloromethylphthalimide, N-bromomethylphthalimide, and mixtures thereof;

c. Reacting the solutions formed in steps (a) and (b) together at atemperature of up to 60C. to form N-mercaptomethylphthalimide;

d. Reacting the N-mercaptomethylphthalimide with adialkylphosphorodithioic acid and formaldehyde to form a compound of theformula:

Page 1 of. g I

' -V UNITED STATES PATENT OFFICE v 56 CERTIFICATE OF CORRECTION PatentNo. 3, 759,949 I Dated September 18, 1973 Inventor(s) Llewellyn W.Fancher and'Jules Kalbfeld It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

In Column 2 line 10, the formula reading should read In Column 3, line22, the-number reading "0.977" should read ----.977--,..

- In Column 3, line, 34, the portion reading "30 formalin" should read---of formalin--.

v In 601mm 4, line 14, the portion reading "Miticide evalutaion test"should be underlined.

--In Column 4, line 37, the portion reading "Systemic evaluation test"should be underscored.

In Column 5, line 7, the portion reading "Internal animal parasitesystemic tests" should be underscored.

Page 2 of -UNITED STATES PATENT OFFICE CERTIFICATE OF LORRECTION PatentNo. 3,759,949 Dated September 18, 1973 lnv n fl Llewellyn W; Fancher andJules Kalbfeld It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

In Column 5, line 13, the worde'lperos" should be underecored,

:Sign ed ahd sealed this 19th day of Ndvember 1974.

(SEAL) Attest:

McG-OY M. GIBSON JR. Y c. MARSHALL DANN Attesting Officer- Commissionerof Patents

2. The process of claim 1 wherein the sodium compound is sodiummethylate.
 3. The process of claim 1 wherein the sodium compound is asodium dispersion.
 4. The process of claim 1 wherein theN-halomethylphthalimide is N-chloromethylphthalimide.